1. Field of the Invention
The present invention relates to an improved process for producing 2-bromopyridine.
2. Description of the Prior Art
2-Bromopyridine is a chemical intermediate for many pharmaceutical and pesticidal products.
This compound has been produced by a variety of processes. These processes include the following:
(a) the Craig diazotization-bromination method wherein 2-aminopyridine is first reacted with HBr and Br.sub.2 to form a solid orange perbromide; then diazotized with sodium nitrite; followed by a reaction with sodium hydroxide to form the desired 2-bromopyridine [see L. Craig J. Am. Chem. Soc., 56, 232 (1934) and Organic Synthesis, Coll. Vol. III, J. F. Wiley, N.Y., p. 136 (1955)];
(b) a modification of the Craig technique wherein 2-aminopyridine is first reacted with HBr and then with Br.sub.2 to yield a perbromide solution, then sodium nitrite and HCl are added to the reaction mixture; after which NaOH is added [see G. I. Mikhailov, Zhur. Priklad. Khim., 27, pages 349-351 (1954) and Chemical Abstracts, 49, 3961, (1955)];
(c) from 2-aminopyridine by diazotization in a dilute solution of HBr and HNO.sub.2 in small yield, the principal product being the corresponding pyridone [see A. E. Chichibabin et al, J. Russ. Phys. Chem. Soc., 46, 1571-89 (1915) and Chemical Abstracts, 10, 2898 (1916)];
(d) by reacting vapors of bromine and chlorine with pyridine in the presence of carbon tetrachloride at elevated temperatures to form 2-bromopyridine and 2-chloropyridine simultaneously (see U.S. Pat. No. 3,153,045 which issued to Thomas on Oct. 13, 1964);
(e) by the direct bromination of pyridine [see Wibaut and Den Hertog, Rec. trav. chim., 51, 385 (1932); McElvain and Goese, J. Am. Chem. Soc., 65, 2230 (1943); Wibaut, Experientia, 5, 337 (1949)].
(f) from N-methyl-2-pyridone with phosphorus pentabromide and phosphorus oxybromide [See Fischer, Ber., 32, 1303 (1899)].
(g) from sodium 2-pyridinediazotate in solution in concentrated hydrobromic acid [see Chichibabin and Tjashelowa, J. Russ. Phys. Chem. Soc., 50, 495 (1918) (Chem. Zentr., 1923, III, 1021)];
(h) from 2-aminopyridine by diazotization with nitrogen trioxide in 40% hydrobromic acid [see Newman and Fones, J. Am. Chem. Soc., 69, 1221 (1947)];
(i) from 2-chloropyridine by reaction with HBr in the presence of a dehydrated organic solvent (see Japanese Patent Public Disclosure No. 103873).
The preferred method for making 2-bromopyridine has been from 2-aminopyridine by the Craig diazotization-bromination technique or a variation thereof. However, there are certain disadvantages associated with the standard Craig technique. First, the cost of HBr is relatively expensive. Furthermore, it is usually necessary to employ a large molar ratio of HBr to 2-aminopyridine (i.e., more than about 4:1). Thus, the HBr reactant contributes a large proportion of the raw material costs for carrying out this reaction. Besides, 2,5-dibromopyridine may be a significant by-product with the Craig technique.
Also, HBr is generally available in 48% by weight aqueous solutions. Thus, batch productivity is decreased substantially because excessive amounts of 48% HBr are required and large volume equipment also is needed.
As a means of decreasing HBr costs, Mikhailov (see above-noted reference) proposed to substitute concentrated HCl in place of about half of the HBr normally used in the Craig technique. Based on relatively crude boiling point analysis, Mikhailov claimed that no 2-chloropyridine was formed as a by-product. However, as can be seen from the experimental Comparisons 5 and 6 below, the presence of 2-chloropyridine in the 2-bromopyridine product made according to his method was established by using more sophisticated analytical methods (i.e., VPC-mass spectral data). 2-Chloropyridine may be an unacceptable contaminant in 2-bromopyridine for certain pharmaceutical and pesticidal applications.
Accordingly, it is an object of the present invention to improve the Craig technique for making 2-bromopyridine by lowering the amount of HBr needed for that diazotization-bromination reaction; yet not use HCl as a substitute. It is a further objective of the present invention to lower costs and increase productivity of this reaction.